Summary

ConclusionWe find that the chromatin interaction profile of a gene-pair is a good predictor of their spatial co-expression. The accuracy of the prediction substantially improves when chromatin interac-tions are described by scale-aware topological measures of the multi-resolution chromatin interaction network. For co-expres-sion prediction, it is necessary to take into account different levels of chromatin interactions from direct interaction between genes (i.e. small-scale) to chromatin compartment interac-tions (i.e. large-scale).

Co-expression Prediction

Topological Measures

The 3D conformation of the genome in the cell nucleus influ-ences important biological processes such as gene expression. Predicting gene co-expression from frequent long-range chro-matin interactions is a challenging task. We address this by char-acterizing the topology of the cortical chromatin interaction net-work using scale-aware topological measures1. We demon-strate that based on these characterizations it is possible to ac-curately predict spatial co-expression between genes in the mouse cortex.

of Chromatin Interaction Network of Chromosome 16

Gene AGene B

Gene C

Co-expression Network

Chromatin Interaction Network

Gene D

3D Structure of Genome

Gene AGene B

Gene C

Gene D

Coronal View of Cortical Layers

Gene A Gene B

Gene CMid Layers

Deep Layer

Expression LevelLow High

Gene D

Gene C

Gen

e A

Gen

e B

Gen

e D

Pred

icti

on

Shortest Path

Jaccard Index

Scale-awareStandard

Hi-C Resolution

Measure

200 kb

Standard Standard

Multi-resolution

Scale-aware Scale-aware

200 kb Multi-resolution

0.65

0.7

0.75

0.8

0.85 Chr1 ChrX

Topological Signature

0 1

B3galt5 - Carhsp1 Thpo

Kcnj6

Igsf11Hmox2

Gpr156

Fstl1

Ece2

Dyrk1a

D16H22S680E

Clcn2

Chrd

Carhsp1B3galt5

Sidt1

Robo1

Tagln3

Zbtb20

Nde1 Abat

Fam55c

Masp1

Cd47

0 1

Scale-aware Jaccard Index (at Medium-Scale)

Abat - Masp1

Reference[1] M. Hulsman, et al., Graph-topological scale-spaces reveal functional information in physical protein interaction networks, Bioinformatics (2014)

Chromatin Interaction Network: Intrachromosomal Hi-C contacts from mouse cortical cells2

Co-expression Network:Spatial co-expression between genes from Allen Mouse Brain Atlas (ABA)3

Scale-aware topological measures

[2] Y. Shen, et al., A map of the cis-regulatory sequences in the mouse genome. Nature (2012)[3] E. Lein, et al., Genome-wide atlas of gene expression in the adult mouse brain. Nature (2007)

Chromatin interactions predict co-expression in the mouse cortex

Ahmed Mahfouz1,2*, Sepideh Babaei1*, Marc Hulsman1,3, Boudewijn PF Lelieveldt2, Jeroen de Ridder1, Marcel Reinders1

Co-expressionChromatin Interaction

1Delft Bioinformatics Lab, Delft University of Technology, 2Dept. of Radiology, Leiden University Medical Center, 3Department of Clinical Genetics, VU University Medical Center*Shared first authorship, a.mahfouz@lumc.nl